Dr. Federico Pelisch
Meiosis is a specialized division in which a single round of DNA replication is followed by two consecutive segregation steps, resulting in daughter cells carrying only one set of chromosomes. Homologous chromosomes segregate in Meiosis I while sister chromatids segregate in Meiosis II, giving rise to haploid gametes. Defects in meiosis are extremely common, but due to their severe consequences, they are not widely observed in populations. Most chromosomal abnormalities in human embryos arise after losing or gaining one or more chromosomes during meiosis. Aneuploid embryos account for at least 10% of human pregnancies and, for women nearing the end of their reproductive lifespan, the incidence may exceed 50%.
Several proteins are involved in the accurate partitioning of chromosomes/chromatids during meiosis. Furthermore, the interactions between these proteins have to be tightly regulated in time and space. Our lab focuses on how protein interactions are dynamically regulated in leading to proper chromosome dynamics during meiosis, with a special focus on the role of the small ubiquitin-related modifier (SUMO). We use a combination of in vivo and in vitro approaches such as proteomics, high- and super-resolution microscopy, biochemistry, and CRISPR/Cas9 genome editing. We mainly use the nematode C. elegans, which provides an excellent model to study meiotic chromosome segregation, as meiosis can be tracked with high time and space resolution (Figure).
We have recently uncovered that assembly of key protein complexes is dependent on the small ubiquitin-related modifier SUMO, through a combination of covalent and non-covalent interactions (i.e. SUMO network). Our current work focuses on three main areas:
1. How SUMO networks are established during meiosis.
2. How desumoylation contributes to chromosome segregation.
3. How sumoylation and phosphorylation concertedly regulate protein dynamics during chromosome segregation.
** Figure Legend: The image depicts a montage of a time-lapse recording of a transgenic C. elegans oocyte (expressing GFP-tagged alpha-tubulin and mCherry-tagged histone) going through Meiosis I. The oocyte was dissected from the worm and imaged using a spinning disk confocal microscope.
Bel Borja, L.; Soubigou, F.; Taylor, S.J.P.; Fraguas Bringas, C.; Budrewicz, J.; Lara-Gonzalez, P.; Sorensen-Turpin, C.G.; Bembenek, J.N.; Cheerambathur, D.K.; and Pelisch, F. PP2A:B56 Regulates Meiotic Chromosome Segregation in C. elegans Oocytes. bioRxiv 2020.06.12.148254; doi: https://doi.org/10.1101/2020.06.12.148254
Pelisch F, Bel Borja L, Jaffray E, Hay R. 2019. Sumoylation regulates protein dynamics during meiotic chromosome segregation in C. elegans oocytes. Journal of Cell Science. https://doi.org/10.1242/jcs.232330
Pelisch, F.; Tammsalu, T.; Wang, B; Jaffray, E.G.; Gartner, T.; and Hay, R.T. SUMO-dependent protein network regulates chromosome congression during oocyte meiosis. Molecular Cell (2017), 65:66-77. PMID 27939944 view paper
Pelisch, F.* & Hay, R.T. Tools to study SUMO conjugation in C. elegans. Methods Mol Biol. 2016;1475:233-56. doi: 10.1007/978-1-4939-6358-4_17. *Sole corresponding author. PMID 27631810
Pelisch, F; Sonneville R; Pourkarimi E.; Agostinho, A.; Blow, J.J.; Gartner, A.; and Hay R.T. Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans. Nature Communications (2014) Dec 5;5:5485. doi: 10.1038/ncomms6485. PMID 25475837 view paper
Pelisch, F*; Pozzi, B; Risso, G; Muñoz, M; and Srebrow, A*. DNA Damage-induced Heterogeneous Nuclear Ribonucleoprotein K SUMOylation Regulates p53 Transcriptional Activation. J. Biol. Chem. (2012), 287(36):30789-30799. PMID 22825850 *co-corresponding authors. view paper